A. Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is the collective term used to describe two chronic, idiopathic gastrointestinal disorders: ulcerative colitis ("UC") and Crohn's disease ("CD"). Although the diseases have distinct pathophysiological characteristics, they are frequently considered together due to several clinical and therapeutic similarities. Several other types of inflammatory conditions of the bowel having known infectious, toxic or ischemic etiology, such as irritable bowel syndrome, infectious diarrhea, rectal bleeding, radiation colitis, and the like, may mimic IBD acutely, because the mucosa of the small and large intestines reacts in a similar way to a large number of different insults. However, if the disease progression is monitored over time, they can be distinguished from IBD by their failure to cause a chronic relapsing and remitting syndrome.
IBD occurs world-wide and is reported to afflict as many as two million people. The course and prognosis of IBD is widely variable. Onset has been documented at all ages; however, IBD predominately begins in young adulthood. The three most common presenting symptoms of IBD are diarrhea, abdominal pain, and fever. The diarrhea may range from mild to severe and is often accompanied by urgency and frequency. In UC, the diarrhea is usually bloody and may contain mucus and purulent matter as well. Anemia and weight loss are additional common signs of IBD. Ten to fifteen percent of all patients with IBD will require surgery over a 10-year period. The risk for the development of cancer is increased in patients with IBD as well, particularly in those with UC. The longer the duration of disease, the higher the risk of developing carcinoma. Patients with UC regularly undergo cancer surveillance by endoscopy after ten years of disease. Reports of an increasing occurrence of psychological problems, including anxiety and depression, are perhaps not surprising secondary effects of what is often a debilitating disease that occurs in people in the prime of life.
B. The Cause(s) of IBD are Unknown
Although the etiology of IBD is unknown, a number of studies have suggested that genetics is important in a person's susceptibility to IBD and that the immune system is responsible for mediating the tissue damage in these diseases. Generally speaking, a failure to down regulate the normal self-limited inflammatory response of the bowel is characteristic of IBD, but it remains unclear what initiates the pathogenic processes and how it may differ, if at all, in UC and CD.
It has also been suggested that a primary abnormality of the immune system and its regulation might serve as primary initiating factors, or that the disease process might be initiated by an infectious agent and the injury is then perpetuated through immune-mediated or other processes. Although the mucosal injury observed during episodes of acute disease can resemble the effects of any of a number of recognized infectious agent, no transmissible infectious agent has been consistently identified with IBD.
Autoimmunity has also been suggested in the pathogenesis of IBD. Evidence to suggest this hypothesis is based on the existence of circulating antibodies that react with unknown alimentary tract antigens of both human and animal origin. For example, human fetal and adult colonic, biliary, skin and vascular epithelial cells, epithelial cell associated components from murine small intestine, rat and human colonic epithelial glycoproteins, intestinal bacterial polysaccharide, and antigens from germ-free rat feces have been described to react with sera from patients with IBD. Other studies demonstrated an increased local IgG response in the colonic mucosa of patients with IBD and other colonic inflammations. The mechanism of this IgG response, the specific local antigens involved, and the role of these antibodies are unknown.
C. Need for Objective Diagnostic Tools
Inflammatory bowel disease poses a clinical and scientific challenge to physicians and researchers. To date most of the diagnostic tools for IBD are quite subjective. Diagnosis depends upon a host of procedures aimed at confirming the suspected diagnosis. The initial symptoms are often confused for non-chronic bowel disorders by physicians unfamiliar with IBD, because the mucosa of the small and large intestines reacts in a similar way to a large number of different insults. Consequently, IBD often goes mistreated and undiagnosed until the disease shows its chronicity which results in referral of the patient to a specialist. The imprecise and subjective nature of endoscopic and radiologic examination can result in a misdiagnosis or indeterminate diagnosis even when the IBD is suspected. Unfortunately, the patient must often suffer as the disease progresses before a definitive diagnosis can be made. In many patients, though, the diagnosis of IBD must still be regarded as indeterminate.
The differentiation between the types of IBD, ulcerative colitis and Crohn's disease, carries important prognostic and therapeutic implications. For example, when colectomy is indicated, the type of IBD involved determines which surgical options are appropriate. Surgery (total colectomy) does represent a cure for the symptoms of UC, though a dramatic one. In CD, surgery is never curative. Continent procedures such as the ileorectal pull-through (mucosal proctectomy) or the Kock pouch may be desirable in UC, but are contraindicated in CD.
Thus, IBD and quite often its treatment affects the lifestyle and functional capabilities of those afflicted. Treatment courses often result in adverse physiologic manifestations which must be balanced against the therapeutic benefit. Any intervention which can improve patients' toleration of their disease and therapeutic program is welcome.
The availability of diagnostic methods that would readily distinguish UC from CD as well as other inflammatory disorders of the bowel would represent a major clinical advance which would aid in therapeutic management of IBD and the design of more specific treatment modalities. In addition specific detection of the disease in prospective parents can be useful in genetic counseling. Accordingly, there has existed a need for convenient and reliable methods of screening for IBD for diagnostic, prognostic and therapeutic purposes.